The proposed work will study regulation of gene expression in nervous tissue, using as tools gonadal and adrenal steroid hormones which regulate neuroendocrine function andinfluence behavior by interacting directly with the brain. The choice of steroid hormones as tools is based on the fact that extensive knowledge exists as to molecular mechanisms of their action on the genome, on the one hand, and as to medically-relevant effects of these hormones on the brain in normal and disease states on the other. Our approach, which employs neurochemical and cell biological techniques, emphasizes the fate of the hormone itself: entry into the brain; intracellular conversion to more active metabolites; binding to presumptive receptors;and transfer to the cell nucleus. We plan to characterize biochemical effects of these hormone-brain interactions on brain enzymes and to use these effects as end-points to show that the hormone-binding sites actually do function as receptors. In so doing, we shall be studying hormone-mediated adaptations of neurochemical systems related to energy metabolism and to the metabolism of presumptive neurotransmitters. An important aspect of these studies will be developmental aspects of hormone-brain interactions. We shall study the ontogeny of the hormone "receptors" in brain and pituitary in relation to the development of functional neuroendocrine and behavioral systems. We shall also study neurochemically the mechanism of the "organizing" influences of gonadal secretions on the fetal and neonatal brain. These studies will enhance our understanding of neuroendocrine control systems and assist in the creation of rational therapies for diseases involving these systems.